The objective of this project is to evaluate the relationship between the serum level of an alpha-2-glycoprotein and macrophage host defense to cancer. Temporal associations between the serum level of this protein and macrophage anti-tumor capacity has been recently documented in animals and humans. Reticuloendothelial activation during tumor growth correlates with an elevation in this protein as detected by bioassay while advanced malignant disease and macrophage dysfunction is associated with severe depletion of this protein. The protein has been isolated and is an alpha-2-acid glycoprotein of large molecular weight which is both thermolabile and highly dependent on heparin for expression of activity. It manifests opsonic and chemotactic properties. Tumor cell entrance into the blood will deplete the opsonin level, and post-operative hypo-opsonemia and RES depression results in decreased resistance to intravenous tumor cell challenge. Antiserum to this protein will inhibit phagocytosis, and the isolated protein (preliminary studies) will inhibit the growth of a transplantable tumor. This project will employ both a bioassay and a recently developed electroimmunoassay for the measurement of opsonin levels in tumor-bearing animals and in humans during malignant disease. Additionally, we will isolate this protein from humans, characterize it, and develop the immunoassay for clinical measurement in patients with malignant disease following immunotherapy. The animal studies will be directed toward further biochemical characterization of this protein; investigating its interaction with macrophage and tumor cell membranes; and analysis of its effect on macrophage killing of tumor cells. Studies will also be continued in animals on the ability of "opsonin" therapy to circumvant post-operative macrophage dysfunction and enhance resistance to tumor growth and spread. The project will lead to a better understanding of the relationship of this protein to macrophage defense against cancer. It will also allow the development of an immunoassay for study of alpha-2-opsonic glycoprotein levels in patients with cancer.